PROJECT SUMMARY (Pharmacokinetics and Bioanalysis Core) The Pharmacokinetics and Bioanalysis core will support both the preclinical and clinical studies. It will conduct the pharmacokinetic analyses of insulin in plasma, cerebrospinal (CSF) and brain tissue in the EcoHIV mouse model. It will also determine levels of antiretroviral (ARV) drugs and glucose levels in plasma, CSF, and brain tissue. In conjunction with the pharmacological results obtained in the EcoHIV model, the core will establish a pharmacokinetic/pharmacodynamic (PK/PD) model relating drug exposures to positive efficacy endpoints. Results from the mouse model will also inform on potential side effects of insulin brain exposure, interaction between insulin and ARV administration, and aide in the choice of CSF markers to follow insulin efficacy in humans. The core will support the clinical studies with bioanalyses of insulin and glucose in CSF and plasma as well as evaluate ARV drugs in plasma from clinical studies to ensure insulin does not alter ARV disposition. Core scientists have extensive experience with pharmacokinetics and bioanalysis including the specific measurements mentioned above.